Sex differences in formation of anti-T-cell antibodies

A NATURALLY occurring thymocytotoxic autoantibody (NTA) has been found in significant titre early in life in NZB mice¹. This antibody is present in almost all NZB mice by 3 months of age, and is associated with an age-dependent loss of T cells in these mice^2-4. NTA may be responsible for an initial loss of suppressor T cells in NZB mice and thereby contribute to the development of autoimmunity. Although other mouse strains (NZW, C57BL/6J, AKR/J, BALB/cJ, and 129) may produce NTA later in life, the prevalence and titre of NTA is much lower than in NZB mice. NTA reacts with brain- and thymus-derived cells as well as thymocytes, but not B cells or non-lymphoid abdominal organs^1-5. In contrast to standard anti-θ serum, NTA can combine with both Thy 1.1 (θ-AKR) and Thy 1.2 (θ-C3H)^1,6. Genetic factors have been implicated in the development of autoimmunity in New Zealand mice^7,8. In addition, X-linked immune response genes have been described for synthetic⁹ and naturally occurring¹⁰ nucleic acids. Moreover, female hybrids (NZB/NZW) develop a more severe disease than males. We therefore undertook the present study to determine the contribution of the X chromosome to the development of NTA.