CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells.

Abstract

SummaryPurified CD4 + lymph node T cells were sorted into two populations on the basis of their expression of CD45RB (CD45RB hi and CD45RB 1~ and injected into congenic severe combined immunodeficient (SCID) mice. After a period of time that was dependent on the number of cells injected, the SCID mice that received CD45RBhi/CD4 + T cells developed a wasting disease that was not seen in SCID mice that received the CD4+/CD45RB 1~ cells or whole lymph node cells. At death, SCID mice that received the CD4 +/CD45RB hi cells had increased spleen and lymph node cellularity compared with normal SCID mice and SCID mice that received the CD4+/CD45RB 1~ T cells. The spleen and lymph node contained CD4 + cells and neither CD8 + nor surface immunoglobulin M-positive cells, plus a population of cells that did not express any of those markers. At necropsy, the SCID mice that received the CD4 +/CD45RB hi cells had significant hyperplasia of the intestinal mucosa with significant lymphoid cell accumulation in the lamina propria. Interestingly, mice that received mixtures of whole lymph node or purified CD4 * cells with CD4 +/CD45RB ~ cells did not develop weight loss, indicating that the unseparated CD4 + population contained cells that were capable of regulating the reactivity of the CD4 +/CD45RB hi cells. utoaggressive immunological reactivity can be driven by CD4 § thymus-derived lymphocytes. For instance, it has been demonstrated that experimental autoimmune encephalomyelitis and diabetes can be induced in normal animals by injecting them with CD4 + T cell clones or lines derived from animals with autoimmune disease of that particular tissue (1-5). Also, T cell reactivity to self-antigens can be demonstrated in normal animals by immunizing them with a closely related antigen in a unique way or by depleting them of a regulatory population (6-8). These data indicate that T cells with specificity for self-antigens exist normally, but that their reactivity is controlled by immunoregulatory mechanisms.It is well appreciated that thymus-derived lymphocytes can be categorized according to the cell surface antigens they express. This has allowed the classification ofdass I or II MHCrecognizing T cells based on their expression of CD8 or CD4 (9). Also, recent data indicate that virgin and memory T cells can be distinguished by their expression of other cell surface markers such as CD44 or CD45 (10-12). The ability to associate T cell function with the expression of a unique array of cell surface determinants is useful in studying the function of these populations in isolation as well as in defined combinations. For instance, Powrie and Mason (13) have separated CD4 + T cells based on their expression of CD45R and injected the resultant subpopulations into congenic, athymic (nude) animals. They found that nude rats injected with congenic CD45Rhi/CD4 + T cells developed wasting disease characterized by inflammatory infiltrates in many organs. Rats injected with unfractionated CD4 + cells (a mixture of CD45R hi and CD45R l~ cells) did n...

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