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Do suppressor T cells become helper T cells?
Immunology Today, voL 5, No. 3, 1984
61
Do suppressor T cells become helper T cells? SIR, In a very interesting discussion (Immunol. Today, 1983, Vol. 4, pp. 275278), Graham Pawelec and his colleagues concluded that the segregation of T lymphocytes into helper (TH) and suppressor (Ts) ceils is by no means final and that the two functional states may and do change with time and with functional requirements. Since they discussed results of in-vitro experiments with clones of T cells, I would like to cite some in-vivo observations which seem to support the same view. There is a clear but hitherto unexplained difference in the relative proportions of T s and T H cells in the bone marrow - their principal site of origin and in the peripheral blood and lymph nodes. Up to 85% of T cells in bone marrow bear the O K T 8 surface antigen and are considered to be the suppressor type, while these cells make up less than 30% o f T lymphocytes in the blood and lymph nodes 1-3. It is hard to believe that this striking difference in their proportion can be accounted for by the short life span o f T s cells. An alternative explanation IS the conversion of I s cells into I n
(-,--
cells alter the cells have left the bone marrow. This could occur in lymph nodes, in the spleen, and possibly also in the lamina propria of the gut where immune signals from all outer and inner surfaces of the body are received. There, T lymphocytes come into contact with macrophages and interdigitating cells, get final and specific instructions regarding mode of action, and transform into T n cells. There is no direct proof for this suggestion but autoradiographic studies have shown that after entering the spleen, T lymphocytes tend to accumulate in close proximity to marginal-zone macrophages and then migrate to the periarteriolar lymphoid sheath where a preferential accumulation of lymphocytes around interdigitating cells is observed 4. This hypothesis offers an explanation for the effects of total lymphoid irradiation (TLI). Both animal studies 5 and clinical experience with Hodgkin's disease 6 and with rheumatoid arthritis 7 have shown that TLI results in a longlasting predominance of immune suppressor activity. Conversion of T s cells into T H cells in the lymph nodes after TLI might be impaired, leaving a predominance o f T s cells in the blood. In conclusion, these oDservanons
allow for an assumption that T s cells may convert to T H cells, while Pawelec and colleagues have shown that the reverse also happens: T n cells, with their limited proliferative capacity, ultimately revert to action as T s ceils. This conforms well to the network concept of regulation among T cells where the presentation of T lymphocytes as suppressor or helper cells is closely related to the requirement for an immune response, that is, to the presence or absence of antigen 8. v MATJAZ ZWITTER
The Institute of Oncology, Zaloika 2, 61000 Ljub~ana, Yugoslavia. References 1 Janossy, G., Tidman, N., Papageorgiou, E. S. etaL (1981).]i Immunol. 126, 1608-1613 2 Poppema, S., Bhan, A. K., Reinherz, E. L. et al. (1981)J. Exp. Med. 153, 30-41 3 Hsu, S. M., Cossman, J. and Jaffe, E. S. (1983)Am. J. Clin. Pathol. 80, 21-30 4 Brelinska, R. and Pilgrim, Ch. (1983) Cell TissueRes. 233, 671-688 5 King, D. P., Strober, S. and Kaplan, H. S. (1981)J. ImmunoL 126, 1140-1145 6 Case, D. C., Hansen, J. A., Corrales, E. et al. (1977)Blood49, 771-778 7 Kotzin, B. L., Strober, S., Engleman,E. G. et aL (1981)N~ Engl.J. Med. 305, 969-976 8 Eichmann, K., Fey, K., Kuppers, R. et al. (1983) ~])nnger~mn. lmmunopathol,b, 7-32
)
Priority of the anti-idiotypic response after antigen administration: artefact or intriguing network mechanism? Jan Cerny and Garnett Kelsoe Immunization triggers at least two specific responses measurable at cellular and humoral levels: the antigen-driven proliferation of idiotype-bearing (idt +) cells," and an autochthonous anti-idt response1. As the expansion of the idt + done(s) is presumed to provide the activating stimulusfor the complementary response, one expects theproliferation of anti-idt clones tofollow the idt + response at an interval equivalent to the time requiredfor lymphocyte activation. However, there have been several reports of an autochthonous anti-idt responsepreceding the expansion of antigen-driven idt + clone(s). In this briefcommentary, we examine these reports and offer some suggestions that may resolve this apparent paradox. W e h a v e studied the kinetics of the p r i m a r y response to phosphorylcholine (PC) in t e r m s of the clonal expansions of b o t h idt ÷ (i.e. T15 +) a n d anti-idt (anti-T15) clones in BALB/c mice given a single dose of antigen 1,2. I n brief, we found that the idt ÷ a n d c o m p l e m e n t a r y anti-idt responses oscillated a b o u t o n e a n o t h e r in a reciprocal fashion, implying m u t u a l regulation based u p o n d e n s i t y - d e p e n d e n t m e c h a n i s m s 2'3. Surprisingly, we consistently f o u n d a n increase in anti-idt activity m e a s u r a b l e within 24-48 h after Department of Microbiology, University of Texas Medical Branch, Galveston, T X 77550, USA.
i m m u n i z a t i o n , thus p r e c e d i n g the e x p a n s i o n of idt + clones b y 1-2 days 1'2. T h e early peak of the anti-idt response was small a n d t r a n s i e n t as c o m p a r e d to the later peaks which followed the a n t i g e n - d r i v e n response (Fig. I). A t first we surmised t h a t this u n e x p e c t e d early peak of anti-idt activity was a technical artefact. W e m e a s u r e d idt + cells as PC-specific p l a q u e - f o r m i n g cells ( P F C ) (inhibitable by anti-idt antisera), w h e r e a s the anti-idt cell response was d e t e r m i n e d as a c h a n g e in the ability of splenocytes to b i n d radiolabelled T E P C - 1 5 protein. It seemed possible t h a t the a p p a r e n t early increase in T15 b i n d i n g was due to residual cell-associated antigen (to © 1984,ElsevierSciencePublishersB.V..Amsterdam 0167 4919/84/$02.00
61
Do suppressor T cells become helper T cells? SIR, In a very interesting discussion (Immunol. Today, 1983, Vol. 4, pp. 275278), Graham Pawelec and his colleagues concluded that the segregation of T lymphocytes into helper (TH) and suppressor (Ts) ceils is by no means final and that the two functional states may and do change with time and with functional requirements. Since they discussed results of in-vitro experiments with clones of T cells, I would like to cite some in-vivo observations which seem to support the same view. There is a clear but hitherto unexplained difference in the relative proportions of T s and T H cells in the bone marrow - their principal site of origin and in the peripheral blood and lymph nodes. Up to 85% of T cells in bone marrow bear the O K T 8 surface antigen and are considered to be the suppressor type, while these cells make up less than 30% o f T lymphocytes in the blood and lymph nodes 1-3. It is hard to believe that this striking difference in their proportion can be accounted for by the short life span o f T s cells. An alternative explanation IS the conversion of I s cells into I n
(-,--
cells alter the cells have left the bone marrow. This could occur in lymph nodes, in the spleen, and possibly also in the lamina propria of the gut where immune signals from all outer and inner surfaces of the body are received. There, T lymphocytes come into contact with macrophages and interdigitating cells, get final and specific instructions regarding mode of action, and transform into T n cells. There is no direct proof for this suggestion but autoradiographic studies have shown that after entering the spleen, T lymphocytes tend to accumulate in close proximity to marginal-zone macrophages and then migrate to the periarteriolar lymphoid sheath where a preferential accumulation of lymphocytes around interdigitating cells is observed 4. This hypothesis offers an explanation for the effects of total lymphoid irradiation (TLI). Both animal studies 5 and clinical experience with Hodgkin's disease 6 and with rheumatoid arthritis 7 have shown that TLI results in a longlasting predominance of immune suppressor activity. Conversion of T s cells into T H cells in the lymph nodes after TLI might be impaired, leaving a predominance o f T s cells in the blood. In conclusion, these oDservanons
allow for an assumption that T s cells may convert to T H cells, while Pawelec and colleagues have shown that the reverse also happens: T n cells, with their limited proliferative capacity, ultimately revert to action as T s ceils. This conforms well to the network concept of regulation among T cells where the presentation of T lymphocytes as suppressor or helper cells is closely related to the requirement for an immune response, that is, to the presence or absence of antigen 8. v MATJAZ ZWITTER
The Institute of Oncology, Zaloika 2, 61000 Ljub~ana, Yugoslavia. References 1 Janossy, G., Tidman, N., Papageorgiou, E. S. etaL (1981).]i Immunol. 126, 1608-1613 2 Poppema, S., Bhan, A. K., Reinherz, E. L. et al. (1981)J. Exp. Med. 153, 30-41 3 Hsu, S. M., Cossman, J. and Jaffe, E. S. (1983)Am. J. Clin. Pathol. 80, 21-30 4 Brelinska, R. and Pilgrim, Ch. (1983) Cell TissueRes. 233, 671-688 5 King, D. P., Strober, S. and Kaplan, H. S. (1981)J. ImmunoL 126, 1140-1145 6 Case, D. C., Hansen, J. A., Corrales, E. et al. (1977)Blood49, 771-778 7 Kotzin, B. L., Strober, S., Engleman,E. G. et aL (1981)N~ Engl.J. Med. 305, 969-976 8 Eichmann, K., Fey, K., Kuppers, R. et al. (1983) ~])nnger~mn. lmmunopathol,b, 7-32
)
Priority of the anti-idiotypic response after antigen administration: artefact or intriguing network mechanism? Jan Cerny and Garnett Kelsoe Immunization triggers at least two specific responses measurable at cellular and humoral levels: the antigen-driven proliferation of idiotype-bearing (idt +) cells," and an autochthonous anti-idt response1. As the expansion of the idt + done(s) is presumed to provide the activating stimulusfor the complementary response, one expects theproliferation of anti-idt clones tofollow the idt + response at an interval equivalent to the time requiredfor lymphocyte activation. However, there have been several reports of an autochthonous anti-idt responsepreceding the expansion of antigen-driven idt + clone(s). In this briefcommentary, we examine these reports and offer some suggestions that may resolve this apparent paradox. W e h a v e studied the kinetics of the p r i m a r y response to phosphorylcholine (PC) in t e r m s of the clonal expansions of b o t h idt ÷ (i.e. T15 +) a n d anti-idt (anti-T15) clones in BALB/c mice given a single dose of antigen 1,2. I n brief, we found that the idt ÷ a n d c o m p l e m e n t a r y anti-idt responses oscillated a b o u t o n e a n o t h e r in a reciprocal fashion, implying m u t u a l regulation based u p o n d e n s i t y - d e p e n d e n t m e c h a n i s m s 2'3. Surprisingly, we consistently f o u n d a n increase in anti-idt activity m e a s u r a b l e within 24-48 h after Department of Microbiology, University of Texas Medical Branch, Galveston, T X 77550, USA.
i m m u n i z a t i o n , thus p r e c e d i n g the e x p a n s i o n of idt + clones b y 1-2 days 1'2. T h e early peak of the anti-idt response was small a n d t r a n s i e n t as c o m p a r e d to the later peaks which followed the a n t i g e n - d r i v e n response (Fig. I). A t first we surmised t h a t this u n e x p e c t e d early peak of anti-idt activity was a technical artefact. W e m e a s u r e d idt + cells as PC-specific p l a q u e - f o r m i n g cells ( P F C ) (inhibitable by anti-idt antisera), w h e r e a s the anti-idt cell response was d e t e r m i n e d as a c h a n g e in the ability of splenocytes to b i n d radiolabelled T E P C - 1 5 protein. It seemed possible t h a t the a p p a r e n t early increase in T15 b i n d i n g was due to residual cell-associated antigen (to © 1984,ElsevierSciencePublishersB.V..Amsterdam 0167 4919/84/$02.00