Colonization of the avian respiratory tract with Mycoplasma gallisepticum results in a profound inflammatory response in the trachea, air sacs, conjunctiva, and lungs. A live attenuated M. gallisepticum vaccine strain, GT5, was previously shown to be protective in chickens upon challenge; however, the mechanisms by which this vaccine and others confer protection remain largely unknown. The current study evaluated several potential correlates of GT5 vaccine-mediated immune protection following challenge with the pathogenic M. gallisepticum strain R low . GT5-vaccinated chickens developed mild tracheal lesions, consisting of few and scattered, discrete, lymphofollicular aggregates in the lamina propria. In addition, low numbers of aggregated B, CD4؉ , and CD8 Mycoplasma gallisepticum is a highly infectious respiratory pathogen affecting poultry. When present in concert with other respiratory pathogens such as infectious bronchitis virus, Newcastle disease virus, Escherichia coli, or Haemophilus paragallinarum, a condition known as chronic respiratory disease results. The clinical signs associated with M. gallisepticum infection in chickens include respiratory rales, nasal discharge, coughing, and occasionally conjunctivitis (20). The most prominent pathological findings include inflammatory lesions in the trachea, air sacs, lungs, conjunctiva, and other tissues such as the oviduct (25). Significant economic losses from M. gallisepticum infection in poultry occur due to reduced egg production and hatchability, as well as downgrading of carcasses (20). Mycoplasma gallisepticum transmission can occur both horizontally through aerosols and vertically through the egg, leading to a rapid spread within the flock. Control programs for M. gallisepticum infection are based on maintaining a commercial breeding stock that is M. gallisepticum free and rearing them in single-aged, all-in/all-out farms. However, in multiple-age production complexes, administration of suitable antibiotic medication is practiced to reduce production losses and egg transmission (18). Eradication by means of vaccination is also one of the preferred methods of control under such circumstances.Previously, bacterins and live vaccines have been commercially used for the control of M. gallisepticum infection in chickens (35). Killed whole-cell M. gallisepticum bacterins reduced the severity of lesions and egg production losses but did not completely prevent M. gallisepticum colonization of the chicken respiratory tract upon challenge (14, 37). At the same time, bacterins fail to provide complete protection against heterologous exposure. Over the past decade, the use of bacterins has been supplanted by more effective live attenuated vaccines. Three live attenuated vaccines (ts-11, 6/85, and F-strain) have been commercialized and have shown a high degree of efficacy in controlling the dissemination of disease (1,6,15,35). Little is known regarding the genetic basis of attenuation in these strains, as well as the immune mechanisms by which protection is con...