Activated type II collagen reactive T cells are not eliminated by in vivo anti-CD4 treatment. Implications for therapeutic approaches on autoimmune arthritis.
Activation of CD4+ T cells plays an important role in type II collagen (CII) induced arthritis (CIA). The CD4+ T cell dependency is demonstrated by anti-CD4 antibody treatment which suppresses CIA in mice if injected before CII immunization. The same anti-CD4 treatment at a later stage does not suppress CIA, despite extensive elimination of peripheral CD4+ T cells. A possible explanation for this discrepancy is that activated T cells might not be as easily influenced by the anti-CD4 antibodies as resting T cells. To address this question, the proliferative capacity of CII reactive CD4+ lymph node (LN) T cells, in mice treated with anti-CD4 antibodies before or after the CII immunization, was analyzed. In mice treated before immunization the capacity of LN cells to proliferate in vitro was markedly suppressed while in mice receiving anti-CD4 treatment after immunization it was retained. Flow cytometric analysis revealed that the anti-CD4 treatment before and after immunization reduced the number of CD4+ LN T cells to the same level. The small population of CD4+ LN cells which were left after anti-CD4 treatment of naive mice all expressed CD44, a marker for previously activated T cells in mice. We propose that activation render CII reactive T cells more resistant to anti-CD4 treatment than virgin T cells are and suggest that the lack of therapeutic effect of late anti-CD4 treatment in CIA does not necessarily implicate that CD4+ T cells are unimportant in that stage of the disease.
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
T J
TJ
Goldschmidt
M
M
Andersson
V
V
Malmström
R
R
Holmdahl
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control; D015704:CD4 Antigens / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D005434:Flow Cytometry; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016201:Receptors, Lymphocyte Homing / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016201:Receptors, Lymphocyte Homing; D003094:Collagen