quite difficult to identify in terms of cloning and structure, it is entirely possible that cells with a cytotoxic function bearing the CD8 marker may play some role in the regulating of CD4+ responses to inhaled proteins and allergens.

One potential role function of CD8+ T cells may be in the regulation and mediation of airway responses in patients with hypersensitivity pneumonitis (HP). While precipitating IgG to the offending antigen in HP is often an important diagnostic and possibly pathogenetic marker, recent studies have identified an enhanced utilization of CD8+ T cells in the bronchoalveolar lavage (BAL) of patients with HP. The function of these CD8+ BAL T cells is unknown, but their potential role as regulators or cytotoxic effectors for HP pathogenesis is intriguing.

OTHER T CELL SUBPOPULATIONS

Subpopulations of CD4+ and CD8+ T cells can also be differentiated according to whether they express the CD45 RA or CD45 RO molecule on their surfaces. CD45 RA and CD45 RO are protein molecules that are expressed as the cells undergo differentiation. One gene codes for each of CD45 RA and CD45 RO; and alternative gene splicing of messenger RNA yields either product as the T cells differentiate. For example, CD45 RA is expressed primarily on naive cells that have not yet been selected for their antigen specificity. The expression of CD45 RO on CD4+ or CD8+ cells is associated with a memory phenotype; it indicates that the cell has been stimulated previously through its antigen receptor. CD45 RA and CD45 RO both participate in the activation of T cells through enzymatic activities related to intracellular signaling.

B LYMPHOCYTES

B lymphocytes, the other major population of lymphocytes, are also involved in the immune and inflammatory reaction that occurs in the airways. B lymphocytes are derived from bone marrow precursors that mature through development in the bone marrow and by exposure to microenvironmental milieus that include a number of growth- and development-related cytokines. The process begins with the selection of B cells for their antigen-specific binding capabilities; these are reflected in membrane IgM on antigen-specific but immature cells. Following selection, the sequential effect of various T cell-derived cytokines, including IL-4, IL-5, and IL-6, drives the undifferentiated but antigen-specific B cells to differentiate further into antibody-secreting plasma cells. This process is accompanied by the specific selection of immunoglobulin isotypes different from the original surface IgM.



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